Generation of β Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene
| Autor: | Maurizio Ferrari, Giovanni Battista Pipitone, Gianvito Martino, Lorenzo Piemonti, Fabio Manenti, Gaia Poggi, Paola Carrera, Rita Nano, Silvia Pellegrini, Marta Tiffany Lombardo, Valeria Sordi, Alessandro Cospito |
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| Přispěvatelé: | Pellegrini, Silvia, Pipitone, Giovanni B, Cospito, Alessandro, Manenti, Fabio, Poggi, Gaia, Lombardo, Marta T, Nano, Rita, Martino, Gianvito, Ferrari, Maurizio, Carrera, Paola, Sordi, Valeria, Piemonti, Lorenzo |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Heterozygote medicine.medical_specialty Endocrinology Diabetes and Metabolism DNA Mutational Analysis Induced Pluripotent Stem Cells Primary Cell Culture Clinical Biochemistry Cell Context (language use) Enteroendocrine cell induced pluripotent stem cells (iPSC) medicine.disease_cause Biochemistry Endocrinology stem cells Insulin-Secreting Cells Internal medicine medicine Humans Induced pluripotent stem cell Gene Cells Cultured Mutation diabetes Chemistry Biochemistry (medical) Cell Differentiation Lipase Molecular biology MODY (monogenic diabetes of the young) In vitro beta cells medicine.anatomical_structure Diabetes Mellitus Type 2 Genetic Techniques Stem cell |
| Zdroj: | J Clin Endocrinol Metab. |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgaa986 |
| Popis: | ContextMaturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by β cell failure. Induced pluripotent stem cells can differentiate into functional β cells. Thus, β cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy.MethodsA genetic study was performed in a patient suspected of monogenic diabetes.ResultsA novel heterozygous pathogenic variant in CEL (c.1818delC) was identified in the proband, allowing diagnosis of MODY8. Three MODY8-iPSC (induced pluripotent stem cell) clones were reprogrammed from skin fibroblasts of the patient, and their pluripotency and genomic stability confirmed. All 3 MODY8-iPSC differentiated into β cells following developmental stages. MODY8-iPSC–derived β cells were able to secrete insulin upon glucose dynamic perifusion. The CEL gene was not expressed in iPSCs nor during any steps of endocrine differentiation.ConclusioniPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and β cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous β cell replacement. |
| Databáze: | OpenAIRE |
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